A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Natalie H. Guley, Joshua T. Rogers, Nobel A. Del Mar, Yunping Deng, Rafiqul M. Islam, Lauren D'Surney, Jessica Ferrell, Bowei Deng, Jessica Hines-Beard, Wei Bu, Huiling Ren, Andrea J. Elberger, Jeffrey G. Marchetta, Tonia S. Rex, Marcia Honig, Anton Reiner

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

Original languageEnglish (US)
Pages (from-to)403-422
Number of pages20
JournalJournal of Neurotrauma
Volume33
Issue number4
DOIs
StatePublished - Feb 15 2016

Fingerprint

Brain Concussion
Skull
Head
Brain Injuries
Brain
Air Pressure
Deceleration
Prosencephalon
Biomechanical Phenomena
Ear
Animal Models
Pathology
Blood Pressure
Pressure

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice. / Guley, Natalie H.; Rogers, Joshua T.; Del Mar, Nobel A.; Deng, Yunping; Islam, Rafiqul M.; D'Surney, Lauren; Ferrell, Jessica; Deng, Bowei; Hines-Beard, Jessica; Bu, Wei; Ren, Huiling; Elberger, Andrea J.; Marchetta, Jeffrey G.; Rex, Tonia S.; Honig, Marcia; Reiner, Anton.

In: Journal of Neurotrauma, Vol. 33, No. 4, 15.02.2016, p. 403-422.

Research output: Contribution to journalArticle

Guley, NH, Rogers, JT, Del Mar, NA, Deng, Y, Islam, RM, D'Surney, L, Ferrell, J, Deng, B, Hines-Beard, J, Bu, W, Ren, H, Elberger, AJ, Marchetta, JG, Rex, TS, Honig, M & Reiner, A 2016, 'A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice', Journal of Neurotrauma, vol. 33, no. 4, pp. 403-422. https://doi.org/10.1089/neu.2015.3886
Guley, Natalie H. ; Rogers, Joshua T. ; Del Mar, Nobel A. ; Deng, Yunping ; Islam, Rafiqul M. ; D'Surney, Lauren ; Ferrell, Jessica ; Deng, Bowei ; Hines-Beard, Jessica ; Bu, Wei ; Ren, Huiling ; Elberger, Andrea J. ; Marchetta, Jeffrey G. ; Rex, Tonia S. ; Honig, Marcia ; Reiner, Anton. / A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice. In: Journal of Neurotrauma. 2016 ; Vol. 33, No. 4. pp. 403-422.
@article{fcdb7a9d150c468f83349158682d7265,
title = "A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice",
abstract = "Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.",
author = "Guley, {Natalie H.} and Rogers, {Joshua T.} and {Del Mar}, {Nobel A.} and Yunping Deng and Islam, {Rafiqul M.} and Lauren D'Surney and Jessica Ferrell and Bowei Deng and Jessica Hines-Beard and Wei Bu and Huiling Ren and Elberger, {Andrea J.} and Marchetta, {Jeffrey G.} and Rex, {Tonia S.} and Marcia Honig and Anton Reiner",
year = "2016",
month = "2",
day = "15",
doi = "10.1089/neu.2015.3886",
language = "English (US)",
volume = "33",
pages = "403--422",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

AU - Guley, Natalie H.

AU - Rogers, Joshua T.

AU - Del Mar, Nobel A.

AU - Deng, Yunping

AU - Islam, Rafiqul M.

AU - D'Surney, Lauren

AU - Ferrell, Jessica

AU - Deng, Bowei

AU - Hines-Beard, Jessica

AU - Bu, Wei

AU - Ren, Huiling

AU - Elberger, Andrea J.

AU - Marchetta, Jeffrey G.

AU - Rex, Tonia S.

AU - Honig, Marcia

AU - Reiner, Anton

PY - 2016/2/15

Y1 - 2016/2/15

N2 - Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

AB - Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

UR - http://www.scopus.com/inward/record.url?scp=84959018590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959018590&partnerID=8YFLogxK

U2 - 10.1089/neu.2015.3886

DO - 10.1089/neu.2015.3886

M3 - Article

C2 - 26414413

AN - SCOPUS:84959018590

VL - 33

SP - 403

EP - 422

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 4

ER -